Hexachlorocyclopentadiene

Repeated dose toxicity: dermal

Administrative data

Endpoint:

short-term repeated dose toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1975

Report date:

1975

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 410 (Repeated Dose Dermal Toxicity: 21/28-Day Study)

Deviations:

yes

Remarks:

Two animals per sex and per dose had their skin abraded. No indication if the substance was held in contact with the skin.

GLP compliance:

no

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Hexachlorocyclopentadiene

EC Number:

201-029-3

EC Name:

Hexachlorocyclopentadiene

Cas Number:

77-47-4

Molecular formula:

C5Cl6

IUPAC Name:

hexachlorocyclopentadiene

Test animals

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: not specified
- Females (if applicable) nulliparous and non-pregnant: not specified
- Age at study initiation: adult
- Weight at study initiation: From 2 to 3 kg
- Housing: individually
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: not specified

ENVIRONMENTAL CONDITIONS
- Temperature (°C): not specified
- Humidity (%): not specified
- Air changes (per hr): not specified
- Photoperiod (hrs dark / hrs light): not specified

Administration / exposure

Type of coverage:

not specified

Vehicle:

ethanol

Details on exposure:

TEST SITE
- Area of exposure: back
- % coverage: 20
- Type of wrap if used: not specified
- Time intervals for shavings or clipplings: one week but more often if necessary

REMOVAL OF TEST SUBSTANCE
- Washing (if done): not specified
- Time after start of exposure: not specified

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 1 mL/kg
- Concentration (if solution): 0.1% w/v or 0.5% w/v
- Constant volume or concentration used: yes

VEHICLE
- Justification for use and choice of vehicle (if other than water): not specified
- Purity: not specified

USE OF RESTRAINERS FOR PREVENTING INGESTION: yes

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

4 weeks

Frequency of treatment:

Once a day, 5 days a week.

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

0 mg/kg bw/day (nominal)

Doses / concentrations 2

Dose / conc.:

1 mg/kg bw/day (nominal)

Doses / concentrations 3

Dose / conc.:

5 mg/kg bw/day (nominal)

No. of animals per sex per dose:

5 animals/sex/dose (including 2 animals/sex/dose with abraded skin).

Control animals:

yes, concurrent no treatment

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Daily

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Daily

DERMAL IRRITATION (if dermal study): Yes
- Time schedule for examinations: Daily

BODY WEIGHT: Yes
- Time schedule for examinations: Weekly

FOOD CONSUMPTION:
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No

FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No

WATER CONSUMPTION: No

OPHTHALMOSCOPIC EXAMINATION: No

HAEMATOLOGY: Yes
- Time schedule for collection of blood: Prior to the start of the study and at Day 23 of the study
- Anaesthetic used for blood collection: No data
- Animals fasted: Yes
- How many animals: All animals

CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: Prior to the start of the study and at Day 23 of the study
- Animals fasted: Yes
- How many animals: All animals

URINALYSIS: Yes
- Time schedule for collection of urine: At Day 23 of the study
- Metabolism cages used for collection of urine: Yes
- Animals fasted: Yes

NEUROBEHAVIOURAL EXAMINATION: No

Sacrifice and pathology:

GROSS PATHOLOGY: Yes

HISTOPATHOLOGY: Yes

Statistics:

Not specified

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Dermal irritation:

effects observed, treatment-related

Description (incidence and severity):

The test substance was severely irritating to the skin upon repeated dermal application at both concentration tested.

Mortality:

no mortality observed

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

Non significant body weight losses were noted in some animals treated at 5 mg/kg bw/d.

Food consumption and compound intake (if feeding study):

not examined

Food efficiency:

not examined

Water consumption and compound intake (if drinking water study):

not examined

Ophthalmological findings:

not examined

Haematological findings:

no effects observed

Clinical biochemistry findings:

no effects observed

Urinalysis findings:

no effects observed

Behaviour (functional findings):

not examined

Immunological findings:

not examined

Organ weight findings including organ / body weight ratios:

effects observed, non-treatment-related

Description (incidence and severity):

Statically significant organ weight differences were observed between the groups but the results were within the historical data of the laboratory for rabbits of this strain and age. These differences were attributed to grouping and the small number of animals.

Gross pathological findings:

effects observed, treatment-related

Description (incidence and severity):

Gross skin changes were observed consisting of fibrosis, escharosis and slight to severe desquamation for both treated groups. No systemic effects were observed.

Neuropathological findings:

not examined

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Description (incidence and severity):

Microscopic examination of the test skin sites revealed acanthosis and hyperkeratosis involving the epidermis in a few animals treated at 1 mg/kg bw/d and most animals treated at 5 mg/kg bw/d. An associated inflammation of the dermis escharosis formation, epidermal ulceration or microabscessation were also observed in some animals. No systemic effects were observed.

Histopathological findings: neoplastic:

no effects observed

Other effects:

no effects observed

Effect levels

1

Key result

Dose descriptor:

NOAEL

Remarks:

systemic

Effect level:

> 5 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

body weight and weight gain

clinical biochemistry

clinical signs

gross pathology

haematology

histopathology: neoplastic

histopathology: non-neoplastic

mortality

organ weights and organ / body weight ratios

urinalysis

2

Key result

Dose descriptor:

LOAEL

Remarks:

local

Effect level:

1 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

clinical signs

dermal irritation

gross pathology

histopathology: non-neoplastic

Target system / organ toxicity

Key result

Critical effects observed:

yes

Lowest effective dose / conc.:

1 mg/kg bw/day (nominal)

System:

integumentary

Organ:

skin

Treatment related:

yes

Dose response relationship:

yes

Relevant for humans:

yes

Applicant's summary and conclusion

Conclusions:

This short-term toxicity study by the dermal route performed on the registered substance allowed to determine a NOAEL(systemic) of 5 mg/kg bw/day and a LOAEL(local) of 1 mg/kg bw/day. The skin was the only identified target organ.

Executive summary:

The repeated dose toxicity of Hexachlorocyclopentadiene by the dermal was evaluated using a method similar to the OECD Test Guideline 410 (non-GLP) with deviations.

Rabbits received applications of 0, 1 or 5 mg/kg bw of Hexachlorocyclopentadiene once a day, 5 days per week, for 4 weeks. Mortality, clinical signs and body weight were recorded. Haematology, blood chemistry and urinalysis were investigated. At the end of the study, surviving animals were subjected to gross necropsy and histopathology.

No mortality was observed as a result of this study. No systemic effects including significant variation of the body weight of treated animals were observed.

The test substance was severely irritating to the skin upon repeated dermal application at both concentrations tested. These findings were confirmed during the gross pathology and histopathology examination. Gross skin changes were observed consisting of fibrosis, escharosis and slight to severe desquamation for both treated groups. Microscopic examination of the test skin sites revealed acanthosis and hyperkeratosis involving the epidermis in a few animals treated at 1 mg/kg bw/d and most animals treated at 5 mg/kg bw/d. An associated inflammation of the dermis escharosis formation, epidermal ulceration or microabscessation were also observed in some animals

There was no change in the blood and urine parameters at the end of the study.

This short-term toxicity study by the dermal route performed on the registered substance allowed to determine a NOAEL(systemic) of 5 mg/kg bw/day and a LOAEL(local) of 1 mg/kg bw/day. The skin was the only identified target organ.